Exciting new research provides fresh hope for significantly delaying the progression of Alzheimer’s disease, potentially extending patients’ quality of life by years following their initial diagnosis.
Alzheimer’s disease stands as a predominant cause of mortality among individuals aged 65 and above, encompassing a staggering 60 to 80 percent of dementia cases and impacting nearly 7 million Americans nationwide.
This devastating disease manifests through a series of progressive cognitive impairments, severely affecting memory, communication skills, and judgment, alongside notable alterations in mood, personality, and general behavior.
Despite its widespread impact on millions, effective treatment options that can meaningfully slow or halt the disease’s progression remain largely absent in the medical landscape.
In response to this pressing challenge, a dedicated team of researchers from the Texas A&M University College of Medicine is pioneering an innovative therapeutic approach aimed at delaying Alzheimer’s progression, with their promising findings recently published in the Journal of Extracellular Vesicles.
Alzheimer’s disease is primarily characterized by the gradual degeneration of neurons in the brain, a phenomenon linked to the abnormal build-up of pathological proteins like amyloid-beta and phosphorylated Tau. Chronic inflammation in the brain also plays a significant role, contributing to the disease’s progression. Amyloid-beta, a fragment derived from the larger amyloid precursor protein crucial for brain development, forms toxic clumps in the brains of affected individuals.
As these amyloid precursor fragments accumulate between neurons, they form what are known as amyloid-beta plaques, disrupting normal neuron functionality. In addition, Tau protein, which is essential for stabilizing and transporting vital molecules within neurons in healthy brains, becomes dysfunctional in Alzheimer’s patients, leading to the formation of neurofibrillary tangles that obstruct the neuronal transport system.
Moreover, Alzheimer’s patients exhibit heightened inflammatory responses in the brain, which exacerbate synaptic loss—these connections are critical for neuronal communication—resulting in increased neuronal damage and cognitive decline.
Madhu LN, a prominent research scientist working alongside Ashok K. Shetty, a respected professor and associate director at the Institute for Regenerative Medicine, has teamed up with fellow researchers to specifically target the persistent neuroinflammation that characterizes Alzheimer’s disease. Their groundbreaking approach harnesses anti-inflammatory extracellular vesicles derived from human induced pluripotent stem cell-derived neural stem cells, strategically targeting the cells that contribute to chronic neuroinflammation.
By either directly engaging with inflammatory pathways or indirectly regulating cellular processes that modulate inflammation within the brain or nervous system, they aim to harness the potent therapeutic potential of neural stem cell-derived extracellular vesicles in combating neurodegenerative diseases.
“The key point is that the secreted factors from human neural stem cells, enclosed in tiny extracellular vesicles released by these cells, could be utilized to treat Alzheimer’s disease through a non-invasive intranasal delivery method,” Shetty emphasizes, highlighting the significance of their findings.
“This approach is effective because the cargo carried by these extracellular vesicles could reduce the neuropathological changes in the brain, offering a promising avenue for treatment,” he continues.
These revolutionary extracellular vesicles could potentially be administered via a simple nasal spray, transforming the way Alzheimer’s treatment could be approached in clinical practice.
To evaluate the efficacy of this potential treatment, Madhu and his colleagues conducted experiments administering these extracellular vesicles to an early-stage Alzheimer’s animal model. Results indicated a notable reduction in brain inflammation, fewer amyloid-beta plaques, and diminished levels of accumulated Tau. Additionally, participants exhibited improvements in cognition, memory, and overall mood.
Notably, the study illustrated that microglia, which are resident immune cells in the brain, effectively incorporated the intranasally administered neural stem cell-derived extracellular vesicles. Microglia play a critical role in maintaining overall brain health by refining synapses, which are specialized junctions promoting neuronal network activity. They are also essential in defending against harmful microorganisms and clearing cellular debris and misfolded proteins such as amyloid plaques.
In the context of Alzheimer’s disease, when microglia interact with amyloid plaques, they initially activate and release various proteins that facilitate inflammation. Although this activation aids in clearing amyloid plaques more swiftly, chronic activation ultimately leads to impaired microglial function, resulting in harm to surrounding neurons and increased neuronal loss over time.
“However, prolonged activation causes them to lose their normal function and begin to harm neurons, leading to progressive neuron loss,” Shetty warns, drawing attention to the delicate balance required for microglial function.
“Such alteration in microglia also prevented the overactivation of astrocytes, another type of brain cell that typically supports neurons but can become harmful in Alzheimer’s disease,” Madhu explains, bringing further insight into the therapeutic implications of their findings.
In a significant advancement, Shetty has filed a patent for the intranasal application of neural stem cell-derived extracellular vesicles, which holds promise for treating Alzheimer’s as well as other neurological and neurodegenerative disorders.
“Our journey to advance the application of this therapy for Alzheimer’s disease is just beginning,” Shetty concludes, expressing optimism for future developments in this vital area of research.
**Interview with Dr. Madhu LN on Revolutionary Alzheimer’s Research**
**Interviewer**: Welcome, Dr. Madhu LN! Thank you for joining us today to discuss your groundbreaking research on Alzheimer’s disease.
**Dr. Madhu LN**: Thank you for having me! I’m excited to share our findings.
**Interviewer**: Your recent study highlights the potential of extracellular vesicles derived from neural stem cells in delaying the progression of Alzheimer’s. Can you explain to our audience what extracellular vesicles are and their importance in your research?
**Dr. Madhu LN**: Absolutely. Extracellular vesicles are tiny membrane-bound sacs released by cells, including neural stem cells. They act like delivery vehicles, carrying proteins, lipids, and RNA to other cells. In our research, these vesicles contain anti-inflammatory factors that can help combat neuroinflammation—a significant contributor to Alzheimer’s disease progression.
**Interviewer**: That sounds promising! How exactly do these extracellular vesicles work to alleviate the symptoms of Alzheimer’s?
**Dr. Madhu LN**: Our approach targets the inflammatory pathways in the brain. The vesicles can either directly engage these pathways or regulate the processes that modulate inflammation. This dual action helps mitigate the neuropathological changes in the brain, such as the accumulation of amyloid-beta plaques and tau tangles, which are central to Alzheimer’s pathology.
**Interviewer**: Your team conducted experiments using these vesicles on early-stage Alzheimer’s animal models. What were the results?
**Dr. Madhu LN**: The results were encouraging! We observed a significant reduction in brain inflammation, fewer amyloid-beta plaques, and lower levels of accumulated tau protein. Moreover, cognitive assessments showed improvements in memory, mood, and overall cognition in these models.
**Interviewer**: That’s remarkable! With these promising results, is there potential for this treatment to be used in humans?
**Dr. Madhu LN**: Yes, we believe so. The non-invasive intranasal delivery method we’re developing could make this treatment accessible and easy to administer. It’s a groundbreaking avenue that could transform how we approach Alzheimer’s therapy in clinical settings.
**Interviewer**: You mentioned the possibility of administering this treatment via a nasal spray. How does that work, and what advantages might it offer?
**Dr. Madhu LN**: The nasal spray allows the vesicles to bypass the blood-brain barrier effectively. This barrier complicates the treatment of many central nervous system disorders. Using a non-invasive delivery method not only makes it easier for patients but also could enhance the uptake of therapeutic agents directly into the brain.
**Interviewer**: Given the rising numbers of Alzheimer’s cases worldwide, what impact do you hope your research will have on patients and their families?
**Dr. Madhu LN**: We hope to provide a new avenue that could significantly delay the onset of symptoms, improve quality of life, and potentially extend the time patients can remain independent. This research is a step toward a future where we may better manage or even halt the progression of Alzheimer’s disease.
**Interviewer**: Thank you, Dr. LN, for sharing these exciting insights. We look forward to seeing how your research progresses in the future.
**Dr. Madhu LN**: Thank you! I appreciate the opportunity to discuss our work.